Myoclonus epilepsy with ragged-red fibers
Nov. 06, 2023
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Inhibitory motor seizures are ictal motor epileptic events of central paresis usually unilateral mono- or hemiparesis while consciousness is intact. They are reported under a number of different names, which may be confusing. Inhibitory motor seizures are contralateral to the epileptogenic region, and they are usually associated with other subjective or objective manifestations (predominantly sensory or motor clonic), which mainly precede but may also occur concurrently with the paresis. The paresis is pyramidal in the majority of cases. Seizures last around 5 minutes, but may also progress into inhibitory motor status epilepticus of many hours or days. Sometimes ictal hemiparesis may take a progressive course following frequent ipsilateral clonic seizures. Nearly all patients also suffer from focal motor (mainly clonic) or focal sensory seizures, which affect the same parts of the body and are more frequent than the inhibitory motor seizures of the same patient. Inhibitory motor seizures affect mostly adults (median of 36 years) with brain structural lesions (mainly tumors). The diagnosis is based on thorough clinical assessment and confirmed with ictal EEG. Brain imaging is mandatory in view of the high incidence of brain structural pathology. Inhibitory motor seizures should be differentiated from nonepileptic attacks, transient ischemic attacks, postictal (Todd) paresis, negative myoclonus, and atonic seizures. Prognosis and management depends on etiology. In this article, the author provides a thorough review of historical aspects and details, nomenclature and classification (which is often problematic), clinical manifestations, pathophysiology, EEG, neuroimaging, and optimal management of patients with inhibitory motor seizures.
• Inhibitory motor seizures commonly start in middle-aged patients, mainly with structural frontoparietal brain lesions.
• They manifest with paresis/paralysis of one side of the body (hemiplegia with or without facial involvement) or one extremity (upper or lower monoplegia). These are often preceded by other objective or subjective ictal symptoms, which may also occur concomitantly with the paresis or independently.
• The seizures last around 5 minutes, but may also progress into inhibitor motor status epilepticus.
• Inhibitory motor seizures are diagnosed with thorough clinical assessment, though documentation is only achieved with ictal EEG.
• Inhibitory motor seizures should be differentiated from postictal (Todd) paresis and nonepileptic transient attacks of paresis. They are also different from negative myoclonus and atonic seizures.
The first reference to ictal paralysis is attributed to Gowers (21; 22), who was of the opinion that “weakness associated with epileptoid seizures may in minor attacks be due to inhibition of the same centres as are discharged in severer attacks” and mentioned a case of Jacksonian epilepsy (typical, right-sided) in which “minor fits consisted of inability to speak or move the right arm or leg, there being no convulsion.” He also described a 40-year-old woman with attacks that
begin with “ticking in the right ear,” and this is followed by a painful sensation “like hot needles running into the skin,” which passes down the side to the leg and foot and, after reaching the toes, returns up the leg and side and is felt in the arm, hand, and tongue. She mumbles and cannot speak for half an hour. There is no motor spasm, but as soon as the sensation is felt in the leg and arm the side becomes extremely weak, so that, although ordinarily able to walk well, she becomes unable to stand and scarcely able to raise the arm (21; 22).
In another 48-year-old patient, “the attacks consisted in ‘pins and needles’ in the left thumb, which passed up the arm to the shoulder and left scapula, with a sense of contraction in the arm. This became powerless, so that she dropped anything that was in the hand” (21; 22).
Jackson refers to Gowers’ view of ictal paralysis, but takes no definite position on it (27):
Post-epileptiform paralysis has been ascribed to inhibition by some medical men whose hypotheses deserve respectful consideration. Gowers believes that discharges in epileptic fits sometimes inhibit; he thinks that temporary paralysis is found in some cases after a purely sensory discharge which does not next discharge motor centres, but inhibits them. In some cases of epileptiform seizures the patient tells us that his arm ‘falls dead,’ there being no spasm in it, whilst the face of the same side is being convulsed. This, so far as I can learn, is a paroxysmal, not a post-paroxysmal paralysis, but possibly it remains for a short time after the convulsion of the face has ceased. I express no decided opinion as to the validity of the inhibition hypotheses. I think it possible that there may be discharge spreading slowly in a motor centre of the middle level, excessive enough: to cause slight after-exhaustion of some of its elements, although not one strong enough to overcome the resistance of lowest motor centres and thereby to produce actual convulsion.
Higier described a patient with ictal hemiparesis and suggested that in certain circumstances the cortical inhibition may predominate over the excitation (24). He later coined the term "status hemiparalyticus" a "paralytic equivalent of epilepsy without disturbance of consciousness” (23).
Holmes reported many cases of negative phenomena in focal epilepsies, mainly in visual epileptic seizures (24). Relevant to inhibitory motor seizures is the following extract of his work:
An interesting fact, not generally recognized, is that convulsive attacks are occasionally replaced by other manifestations, the most common of which is a sudden but transient paresis of that portion of the limb which in other attacks is involved in the clonic spasms. Usually the primary paresis appears in the part in which the spasms commence, but it may affect another region the cortical representation of which is adjacent to the site of discharge; in a case recorded by Hughlings Jackson, for instance, clonic movements of the face were immediately followed by paralysis of the hand of the same side. The following case is a good example of one in which at times defect or negative symptoms only occurred. The patient received a gunshot wound at his head in the region of the posterior end of the second left frontal convolution. Some months after being wounded he began to have epileptiform seizures of the Jacksonian type. …. Sometimes, however, attacks occurred in which there were neither tonic nor clonic spasms, or movements of any kind; he simply lost power suddenly and without any warning in the hand. If reading, his book might fall unexpectedly, or his cane might drop from his hand as he walked. The loss of power was complete for a time, but after a few minutes voluntary movement returned and gradually reached the normal. I have seen several other patients with Jacksonian motor epilepsy who were subject to similar sudden transient palsies of the limb or segment of the limb in which at other times the convulsion commenced. The immediate cause of this palsy is doubtful. Higier, who described one case, suggests that in certain circumstances the cortical inhibition of the antagonists may predominate over the excitation. It is difficult to explain it by this hypothesis; it seems more likely that it is due to a primary inhibition instead of waves of excitation spreading over the cortical motor elements, a change perhaps similar to that which causes loss of consciousness in epilepsy and the sudden relaxations of the muscles leading to "falls," which often occur in it. Such observations show that a local lesion producing a functional instability of part of the so-called motor cortex of the brain may, in addition to predisposing to local epileptiform phenomena, which are frequently followed by temporary loss of power in the convulsed part, be the immediate cause of such negative symptoms as a primary transient paralysis of regions of the body represented in its neighbourhood.
SAK Wilson (better known for his eponymous “Wilson disease”) is probably the first to use the name “inhibitory epilepsy” and meticulously described one of his patients during repetitive attacks of transient left-sided sensory loss and hemiparesis (62):
The attack commences by a sensation of tingling, of formication, of ‘wires’ in the left fingers and hand… At the same time as the numbness appears patient loses all power in his arm and leg. Anything he has in his hand be will let drop; he will be unable to pick anything up with the fingers. In a second or two the loss of power in the left arm and hand is absolute and he is quite unable to move it. Similarly with the leg, he is completely unable to move it at any joint… The duration of this combined numbness and loss of power may be merely a minute or two, or as long as 20 minutes. When the attack passes off recovery of power is usually simultaneous in arm and leg.
Lennox and Lennox described an
11-year-old boy who began to have seizures at the age of 8 months. Following a different type of seizure initially, the boy had seizures commencing with a “queer smile,” slumping to the right with weakness or paralysis of the right arm, and in some attacks inversion of the right eye. Puffiness of the right face might precede an attack… The right-sided weakness would persist for 15 minutes to several hours during which he would appear dazed or be briefly unconscious... A convulsion or convulsive movements never preceded the paresis (34).
However, it was Penfield and his associates (44; 46; 45) and later the investigators of the Cleveland Clinic Foundation in Ohio (36; 35; 37; 40) who documented various types and aspects of negative responses and their localization in patients undergoing neurosurgical assessment.
Nomenclature and classification. There is a significant confusion of the nomenclature used to describe inhibitory motor seizures, a matter that has to be addressed by the International League Against Epilepsy (ILAE). By definition, these should be epileptic seizures of central origin that manifest with inhibition (weakness) of motor activity. Inhibitory motor seizures are not synonymous with negative motor seizures, negative myoclonic seizures (negative myoclonus), atonic seizures, or postictal (Todd) paresis. Negative motor seizures manifest with motor arrest defined only by the inability to conduct voluntary movements or praxis, even though muscle power and tone, consciousness, and cognitive functions are relatively intact (ictal apraxia) (25). Arrest of movements predominantly caused by weakness and atonia of the affected limbs is not considered a negative motor seizure. The name negative motor seizures has been coined because of its similarity with the negative motor response, which consists of cessation of the voluntary tonic muscle contraction or the rapid alternating movements (wiggling of the tongue from side-to-side, rapid alternating horizontal or vertical eye movements, rapid alternating hand or foot movements) without loss of awareness, produced by means of high-frequency electric cortical stimulation of the frontal lobe negative motor areas (25).
Inhibitory motor seizures are also different from atonic seizures, which by definition are a manifestation of loss or diminution of muscle tone only.
See MedLink Neurology articles on Atonic seizures, Myoclonic-atonic seizures, Acute hemiplegia in childhood, Myoclonus, and Hemiplegic migraine. Inhibitory motor seizures are not mentioned in most of the ILAE classifications, including the more recent reports (04; 11; 17; 18; 51). Only the ILAE Task Force classifies them under focal neocortical seizures without spread (Table 1) and clarifies: “Inhibitory motor seizures are not a unique seizure type. The clinical manifestation merely represents the function of the involved cortex, just as focal motor seizures and unformed visual hallucinations reflect seizures in precentral gyrus and calcarine cortex” (15).
• With elementary clonic motor signs
Also, inhibitory motor seizures are not specifically cited in the ILAE glossary (07). The only possible reference to them is the following:
MOTOR: Involves musculature in any form. The motor event could consist of an increase (positive) or decrease (negative) in muscle contraction to produce a movement. Unless noted, the following terms are adjectives modifying “motor seizure” or “seizure” (eg, “tonic motor seizure” or “dystonic seizure”), and whose definitions can usually be understood as prefaced by “refers to.”
According to the 2014 ILAE “Epilepsy diagnosis” manual, a negative motor feature is characterized by reduced motor activity (11).
• A negative myoclonic feature involves an interruption in normal tonic muscle activity for 500 milliseconds or less, without evidence of preceding myoclonus.
• An atonic feature involves sudden loss or diminution of muscle tone without apparent preceding myoclonic or tonic activity. This lasts greater than 500 milliseconds but less than 2 seconds. It may involve the head, trunk, jaw, or limb musculature.
• A hypomotor feature involves a decrease in amplitude, or rate or arrest of ongoing motor activity.
The instruction manual for the ILAE 2017 operational classification of seizure types proposes that the term “akinetic” (arrest of movement) should be characterized as “focal behavior arrest, generalized absence” (17).
Furthermore, in the updated ILAE report of definition and classification of status epilepticus, “ictal paresis (ie, focal inhibitory status epilepticus)” is listed as a type of focal motor status epilepticus with no details (59).
Author’s comment. This article is a thorough and objective review of inhibitory motor seizures. Emphasis is on focal inhibitory motor seizures. Because of the significant confusion on nomenclature and classification, detailed clinical vignettes from the literature are presented and exact quotations of published reports are given. Inhibitory motor seizures are described and reported under a number of different names, such as “nonconvulsive seizure paralysis,” “hemiparetic seizures,” “ictal hemiparesis,” “ictal paralysis,” “inhibitory epilepsy,” “akinetic seizures,” “negative” or “atonic seizures,” and so forth. As an example of misperception, the characterization of these seizures as “atonic seizures” is unjustifiable because in a significant number of patients with ictal hemiparesis, there is cortical pyramidal hemiparesis as documented by the involvement of the face (paresis of the lower facial muscles) and ipsilateral increase of tendon reflexes (31). This also has significant implications on pathophysiology, which appears to be different between ictal focal paresis and atonic seizures as indicated by the different populations affected. Atonic seizures (loss of tone) occur mainly in children with epileptic encephalopathies, whereas hemiparetic seizures occur mainly in adults with focal brain structural lesions. Also, the term akinetic (inability to move) should be abandoned because akinesia may be due to many causes of epileptic or nonepileptic origin. Finally, this article is not an attempt to classify them in accordance with their different types based on focal/generalized and mechanistic criteria, which may be considered by the ILAE Commissions on Classification and nomenclature.
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